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Effects of dietary cholesterol and simvastatin on cholesterol absorption and synthesis (CAS) in Smith‐Lemli‐Opitz syndrome (SLOS)
Author(s) -
Chan YenMing,
Merkens Louise,
Roullet JeanBaptiste,
Connor William E.,
Steiner Robert D.,
Jones Peter J.H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a340-d
Subject(s) - smith–lemli–opitz syndrome , cholesterol , simvastatin , medicine , cholesterol synthesis , endocrinology , cholesterol lowering , absorption (acoustics) , chemistry , biochemistry , enzyme , 7 dehydrocholesterol reductase , reductase , physics , acoustics
The objective of this study was to evaluate the effects of dietary cholesterol and statins (ST) on CAS in children with SLOS. A high cholesterol (HI) diet (200–400mg/day of cholesterol) was given to 5 SLOS subjects and a HI diet with ST (HI+ST) (0.1–1.0mg/kg of ST) was administered to 4 SLOS subjects. Three SLOS subjects were fed a low cholesterol (LO) diet (<15 mg cholesterol/1,000 kcal). Dietary phases were at least 4 weeks in duration. Four SLOS subjects were given an oral dose of 13 C‐cholesterol and intravenous injection of D 7 ‐cholesterol to assess cholesterol absorption (ABS) at the end of each phase. D 2 O was administrated orally to 10 SLOS subjects at the end of each phase to measure cholesterol fractional synthesis rate (FSR). CAS was assessed using isotope ratio mass spectrometry (IRMS). HI+ST feeding tended to decrease ABS as compared to HI and LO diets (27.0%, 9.1% and 31.8% for HI, HI+ST and LO, respectively). FSR was lower (P=0.0003) with HI and HI+ST feeding as compared to LO diet (1.4±0.9%, 0.8±1.1%, and 4.8±1.0% for HI, HI+ST and LO, respectively). These findings show feasibility of measuring CAS with stable isotopes in SLOS. ABS may be reduced with ST administration in children with SLOS. HI diet with or without ST lowers FSR in SLOS. The present results support the use of HI diet or HI diet + ST as potential therapy for SLOS. ( Sponsored by NIH) .